In an ongoing NCI contracted study, the authors have demonstrated that simultaneously administered intravesical and percutaneous BCG immunotherapy significantly (p equals 0.029, chi square) decreases the rate of recurrence of transitional cell carcinoma compared with controls. The duration of protection afforded by BCG immunotherapy, and the optimum dose, route, and frequency of BCG administration remain to be determined and are the primary objectives of this proposal. In addition, utilizing a murine bladder cancer model we have demonstrated that excessive BCG administration can impair the antitumor response or even enhance tumor growth, as has been seen by other investigators with different tumor models. It is critical, therefore, that the optimal dose and frequency of BCG immunotherapy be determined while cautiously avoiding excessive BCG administration. Since several biological systems are involved, it is likely that optimal BCG administration will vary from patient to patient. In an effort to develop appropriate monitors of the immune response which may be used to guide effective BCG immunotherapy, we propose to systematically monitor skin test reactivity to PPD, trychophytin, and candida antigens, leukocyte migration and adherence inhibition to bladder tumor and BCG antigens, humoral immunity to bladder tumor and BCG antigens as measured by solid phase radioimmunoassay, serum blocking factors, and serum anti IgG factors.